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October 17, 2005

Making Progress on Nanoscale Thermal Therapy

Raising the temperature of human tissue by a mere 5°C can stop all normal cellular activities and lead to cell death through a process known as thermal ablation. Several groups of investigators are developing nanoparticles and carbon nanotubes as intracellular nanoscale heaters for use in this cancer therapy. Now, two papers from a collaborative group led by researchers at Triton BiosSystems (Chelmsford, MA), provide further evidence that targeted magnetic nanoparticles, heated with an oscillating magnetic field, may be capable of killing tumors in living animals.

Reporting its work in the journal Clinical Cancer Research, a team that included Robert Ivkov, Ph.D., at Triton BioSystems, and Gerald DeNardo, M.D., at the University of California, Davis, demonstrated that magnetic iron oxide particles linked to an antibody that recognizes a molecule on the surface of certain types of cancer cells can exit the bloodstream and bind to the targeted tumor cells. The investigators used an antibody labeled with the radioactive element indium-111 so that they could follow the uptake of the targeted nanoparticle by breast cancer tumors grown in laboratory mice.

The ability to track the nanoparticles also enabled the researchers to determine the optimal time to begin thermal ablation therapy corresponding to the time when tumor accumulation of the nanoparticles reached its peak. Applying an oscillating magnetic field at that time produced significant tumor size reduction, according to the investigators.

In a second paper in the same journal, the researchers showed that animals could be exposed safely to the high-amplitude alternating magnetic field that is needed to heat the nanoparticles for thermal ablation therapy. The key, the researchers found, is to pulse the oscillating magnetic field with sufficient frequency so that heat does not build up in tissues that have not accumulated the magnetic nanoparticles. Using a pulsed magnetic field appears to produce no ill effects in mice.

Since these studies were conducted, the Triton investigators have begun using an anti-Ep-CAM (epithelial cell adhesion molecule) antibody that it licensed from a company that had already conducted human phase I clinical trials with the antibody for another application. The Triton team has also refined and improved its magnetic nanoparticle manufacturing processes to make particles that produce over seven times more heat per nanoparticle. The company anticipates beginning human clinical trials using these improved nanoparticles linked to the anti-Ep-CAM antibody in 2006.

These studies are detailed in two papers titled, "Development of tumor targeting bioprobes (¹¹¹In-chimeric L6 monoclonal antibody nanoparticles) for alternating magnetic field cancer therapy," and "Application of high amplitude alternating magnetic fields for heat induction of nanoparticles localized in cancer." Abstracts of both papers are available through PubMed.
View abstract 1. View abstract 2.


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